Published 4:00 am, Tuesday, April 18, 2006

An osteoporosis drug already in widespread use works just as well at preventing breast cancer among older, high-risk women as the controversial drug tamoxifen, but with fewer life-threatening side effects, according to results of a national study released Monday.

The findings could create a new preventive option for women who have shied way from tamoxifen -- the only drug now approved for preventing breast cancer in post-menopausal women -- because of the potential risk of developing uterine cancer or fatal blood clots.

"This is definitely a step forward in our long-term hopes to prevent breast cancer," said Lou Fehrenbacher, an oncologist at Kaiser Permanente Vallejo Medical Center who oversaw the drug trial for Kaiser's Northern California region. "This is something that may be an alternative for women who are at high risk for getting breast cancer. I think there will be individuals who will be tempted to give this a try and physicians who will be tempted to prescribe it."

The five-year study of nearly 20,000 women, overseen by the National Cancer Institute, showed that taking the drugs tamoxifen and raloxifene cut by half the chances of developing breast cancer for post-menopausal women who had serious risk factors.

Of the 9 million to 10 million American women who are at high risk -- meaning they have a greater than 2 percent chance of developing breast cancer over the next five years -- at least 2 million would benefit from taking one of the two drugs, researchers said.

But prescribing, and taking, tamoxifen has been a difficult choice for doctors and patients because of the rare but dangerous side effects associated with the drug. In the National Cancer Institute study, raloxifene, which has been used to treat osteoporosis in older women, had the same positive results in preventing breast cancer as tamoxifen, but with fewer cases of uterine cancer and blood clots.

Study participants who were taking raloxifene reported 36 percent fewer cases of uterine cancer than those on tamoxifen. The women on raloxifene reported 29 percent fewer cases of serious blood clotting. Raloxifene also reduced by about 21 percent the risk for developing cataracts, another side effect of tamoxifen.

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"With tamoxifen, it put women in a very difficult situation of balancing really scary problems," said Dr. Hope Rugo, director of breast oncology clinical trials at UCSF. "Now you can take raloxifene. It may be that your risk of blood clots and uterine cancer is a little higher than if you didn't take anything at all, but it's markedly less than if you took tamoxifen. You want to get a drug that is good and has less serious side effects, and we've definitely got that now."

Eli Lilly and Co., which manufactures raloxifene for osteoporosis treatment under the brand name Evista, will seek approval from the Food and Drug Administration to sell the drug for breast cancer prevention, the company announced Monday.

Doctors said they expect some patients will seek immediate prescriptions for raloxifene, although they noted that not everyone who is now taking tamoxifen should switch drugs, especially if they have been on tamoxifen for several years with no apparent side effects.

The next step in the research on preventing breast cancer will be a study that is set to start this fall, analyzing the difference between raloxifene and drugs known as aromatase inhibitors, which are not approved for preventing breast cancer among post-menopausal women.

Aromatase inhibitors are hormones that block the production of estrogen in post-menopausal women, thereby potentially halting the creation and growth of breast cancer cells, which rely on estrogen. Aromatase inhibitors have been used to treat women who have already developed breast cancer, but they have not been approved for cancer prevention.

Raloxifene and tamoxifen are what are known as "selective estrogen response monitors" -- drugs that mimic estrogen in some cases and prevent estrogen from mingling with cells in others. Both drugs are effective in reducing the effects of estrogen on breast cancer cells, but tamoxifen acts like estrogen in the uterus and bloodstream, increasing chances of developing uterine cancer and blood clots.

"Raloxifene and tamoxifen are like putting a plug in a keyhole, so estrogen can't turn the lock," said Fehrenbacher, the Kaiser oncologist. "Aromatase inhibitors are essentially throwing away the keys."

Despite the generally favorable results of the National Cancer Institute study, physicians and breast cancer activists alike noted Monday that both tamoxifen and raloxifene increase the rates of uterine cancer and blood clots among otherwise healthy women.

"We're very concerned that the ultimate result will be disease substitution instead of disease prevention," said Barbara Brenner, executive director of San Francisco-based Breast Cancer Action. "This whole approach to prevention involves treating risk as a disease, which means a lot more people will be getting a lot more drugs, and we don't know the long-term results of this."

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